AWMSG APPRAISAL PROCESS FREQUENTLY ASKED QUESTIONS

Transcription

1 AWMSG Appraisal Process: Frequently Asked Questions AWMSG APPRAISAL PROCESS FREQUENTLY ASKED QUESTIONS These questions and answers should be read in conjunction with the following documents: AWMSG appraisal principles & process flowchart AWMSG appraisal process flowchart AWMSG process for industry engagement AWMSG exclusion criteria AWMSG guidance notes for completing Forms A, B & C Form A initial information Form B full submission Form C limited submission Guidelines for appraising medicines Independent Review (IR) Process Agreement between the Association of British Pharmaceutical Industry (ABPI) and the All Wales Therapeutics and Toxicology Centre (AWTTC) on guidelines for the release of company data into the public domain during an appraisal This document aims to provide answers to frequently asked questions and has been separated by the following categories: GENERAL INFORMATION... 5 What is the remit of AWMSG in relation to appraisals?... 5 What is the remit of the All Wales Therapeutics and Toxicology Centre (AWTTC) in relation to appraisals?... 5 What is the remit of the New Medicines Group (NMG) in relation to appraisals?... 5 Is the membership of AWMSG and NMG public?... 5 Does AWMSG appraise a medicine if it has been appraised by the Scottish Medicines Consortium (SMC)?... 5 What is the relationship between AWMSG appraisals and those of the National Institute for Health and Care Excellence (NICE)?... 5 Is NICE advice regarding highly specialised technologies (HSTs) mandatory in Wales?... 6 What if NICE appraises a medicine but does not recommend its use on the grounds of lack of cost-effectiveness, but the medicine is available to patients living in England via alternative commissioning routes (including the Cancer Drugs Fund)?... 6 What communication links exist between the pharmaceutical industry and the All Wales Therapeutics and Toxicology Centre (AWTTC)?... 6 How does the AWMSG appraisal process impact on individual prescribers?... 6 Page 1 of 21

2 All Wales Medicines Strategy Group How are potential appraisals identified?... 6 What are the criteria for deciding whether a medicine undergoes an appraisal?... 6 What if the criteria for appraisal by AWMSG are not met?... 7 What approach is taken when a medicine has multiple indications?... 7 Can the applicant company request appraisal of a medicine for part of the licensed indication or in a particular patient population?... 7 What if the submission relates to a life-extending, end-of-life medicine?... 7 Why is the AWMSG Policy on Appraising Life-Extending, End-of-Life Medicines not included in the new process for appraising orphan, ultra-orphan medicines and medicines developed specifically for rare diseases?... 7 Does AWMSG appraise biosimilar medicines?... 8 Does AWMSG consider equity when appraising a medicine?... 8 How does AWMSG prioritise appraisals?... 8 When is the appraisal date confirmed?... 8 If the AWMSG Steering Committee decides an appraisal is required, what is the timescale?... 8 When is the scope of the appraisal clearly defined?... 8 Who do I contact for clarification of the appraisal process or to address any outstanding issues?... 9 APPRAISAL SUBMISSION FORMS... 9 What is the role of Form A?... 9 When should Form A be submitted?... 9 Does the Summary of Product Characteristics (SPC) need to be submitted with Form A?... 9 What is the timescale for submitting Form B or C?... 9 Does the All Wales Therapeutics and Toxicology Centre (AWTTC) accept unlicensed comparators?... 9 What if the comparator medicine has an associated simple Patient Access Scheme?... 9 Does the All Wales Therapeutics and Toxicology Centre (AWTTC) accept data relating to a licensed comparator outside its licensed dose? Can the applicant company submit commercial/academic in confidence data? What documents will be uploaded to the AWMSG website prior to the AWMSG meeting? Are the completed submissions (Form A, Form B or Form C) posted on the AWMSG website? What is the role of Form B/C? How does a company know if a medicine requires a full (Form B) or limited (Form C) submission? Is guidance available on how to complete Form A, Form B and Form C? Where can I find Welsh unit cost data? Can additional information be provided to the All Wales Therapeutics and Toxicology Centre (AWTTC) after submission of Form B/C? Would a request for a limited submission (Form C) preclude the need for a full submission (Form B)? What if the Form A meets the criteria for a limited submission and the manufacturer has indicated in Form A that they wish to submit a WPAS? Is the process for considering limited submissions (Form Cs) different to that for full submissions (Form Bs)? What are the consequences if a submission (Form A, Form B or Form C) is requested by the All Wales Therapeutics and Toxicology Centre (AWTTC) but not received within the appropriate timelines? November 2015 Page 2 of 21

3 AWMSG Appraisal Process: Frequently Asked Questions APPLICANT COMPANY INPUT INTO APPRAISAL PROCESS Does the applicant company have an opportunity to preview the AWMSG Secretariat Assessment Report (ASAR) before it is provided to the New Medicines Group (NMG) members? Does the applicant company have an opportunity to preview the Preliminary Appraisal Recommendation (PAR) before it is provided to AWMSG members? What is the role of the applicant company in relation to the process for appraising orphan, ultra-orphan medicines and medicines developed specifically for rare diseases? Does the applicant company have an opportunity to preview the final AWMSG Secretariat Assessment Report (ASAR) before it is provided to AWMSG members? THE PATIENT/CARER VIEW How can patients/carers/patient organisations directly input into the AWMSG appraisal process? Are all appraisals by AWMSG held in public? Will the completed patient/carer questionnaires be posted on the website? How are patient organisations identified and invited to make a submission? Why should you, as a patient/carer/patient organisation, provide your views? What should I do if I have any queries or want to learn more about the AWMSG appraisal process? Is there a forum for liaison between AWMSG and patient support groups? CLINICAL EXPERTS What is the role of the clinical expert? How are clinical experts selected? In what form is the clinical expert opinion provided? Are clinical experts asked to declare any interests? Can clinicians do anything to encourage appraisal by AWMSG, particularly if the pharmaceutical industry has not engaged in the appraisal process? THE NEW MEDICINES GROUP (NMG) MEETING Is the applicant company involved in the New Medicines Group (NMG) meeting? 16 What is the role of the Lead Assessor at NMG? Is the applicant company informed of the New Medicines Group (NMG) Preliminary Appraisal Recommendation (PAR)? Can the New Medicines Group (NMG) request additional data or seek clarification on any issue and adjourn the preliminary appraisal? THE AWMSG PUBLIC MEETING What information is considered by AWMSG when making their recommendation? How often are AWMSG meetings held? When are the Preliminary Appraisal Recommendation (PAR) and the company response to the PAR (CR/PAR) posted on the AWMSG website? Is the applicant company involved in the AWMSG meeting? What are the implications of a positive/negative AWMSG recommendation? What is the context of the AWMSG appraisal? How is the appraisal process conducted at the meeting? Who is involved in the decision making process? Are all appraisals by AWMSG held in public? COMMUNICATION POST AWMSG MEETING What happens after a decision has been reached by AWMSG? What are the timelines for Ministerial ratification of an AWMSG Final Appraisal Recommendation (FAR)? Page 3 of 21

4 All Wales Medicines Strategy Group How is the applicant company notified of Ministerial ratification of an AWMSG Final Appraisal Recommendation (FAR)? How is NHS Wales notified of the AWMSG Final Appraisal Recommendation (FAR) and Ministerial ratification? What role does the applicant company have in communicating the AWMSG recommendation? What happens if final Technology Appraisal Guidance from the National Institute for Health and Care Excellence (NICE) becomes available for a medicine that has been appraised by AWMSG? IMPLEMENTATION Is the AWMSG recommendation to the Service binding? Will extra funding be available to support the Ministerial decision? How will the Minister s decision be implemented? Will the industry have a role in implementing AWMSG recommendations? How will the implementation of AWMSG recommendations, once ratified by the Minister, be monitored across NHS Wales? INDEPENDENT REVIEW (IR) Is there a route for an applicant company to follow if they are unhappy with the outcome of an appraisal? How soon after receiving confirmation of the AWMSG Final Appraisal Recommendation (FAR) will the applicant company need to request an independent review (IR)? What does the applicant company need to do to trigger the independent review (IR) process? What is the procedure to address concerns relating to process? What is the procedure to address complaints relating to scientific disputes? Can the applicant company have access to the transcript of the AWMSG meeting at which the original decision was made? Who sits on the independent review (IR) panel? What are the responsibilities of the applicant company? Will the applicant company attend the independent review (IR) hearing? What happens at the independent review (IR) hearing? When and how are the decisions of the independent review (IR) panel communicated? What happens if an independent review (IR) is upheld? What happens if an independent review (IR) is rejected? If the independent review (IR) is rejected, does the applicant company have any other course to challenge the decision? What happens if new data becomes available that would significantly impact on the decision that has been made? What is the status of the AWMSG recommendation whilst an independent review (IR) is being progressed? UPDATING OF AWMSG ADVICE How regularly will the recommendations of AWMSG be reviewed? AWMSG Secretariat: All Wales Therapeutics and Toxicology Centre Academic Centre, University Hospital Llandough, Penlan Road, Penarth, Vale of Glamorgan CF64 2XX Tel: AWTTC@wales.nhs.uk November 2015 Page 4 of 21

5 AWMSG Appraisal Process: Frequently Asked Questions GENERAL INFORMATION What is the remit of AWMSG in relation to appraisals? AWMSG makes recommendations to the Minister for Health and Social Services in relation to the use of new medicines within NHS Wales. Initially the AWMSG appraisal process focused on high-cost medicines (i.e. those costing > 2,000 per patient per annum). In April 2007, the Minister for Health and Social Services increased AWMSG s capacity to review new medicines up to a total of 32 appraisals per year. These comprised of not only highcost medicines, but also new cardiovascular, malignant disease and immunosuppressant medicines. In December 2009, the Minister for Health and Social Services announced that funding would be available from April 2010 for AWMSG to broaden its remit to appraise ALL new medicines not on the National Institute for Health and Care Excellence (NICE) work programme. The implementation date for the broadened process was 1 October To avoid duplication of effort, AWMSG would not normally consider undertaking an appraisal if NICE intends to publish final technology appraisal advice (STA or MTA) for the same medicine and indication(s) within 12 months of the date of marketing authorisation. AWMSG advice is interim to that of NICE, should NICE subsequently publish guidance as an STA or MTA. NICE clinical guidelines are not mandatory within NHS Wales. In addition to new medicines receiving their first licence, new indications and formulations of previously licensed medicines can also be considered. What is the remit of the All Wales Therapeutics and Toxicology Centre (AWTTC) in relation to appraisals? AWTTC provides professional and administrative support to AWMSG. AWTTC critiques the information provided by the applicant company together with any other relevant publically available information to produce the AWMSG Secretariat Assessment Report (ASAR) which is considered by the New Medicines Group (NMG) and AWMSG alongside other relevant documentation. What is the remit of the New Medicines Group (NMG) in relation to appraisals? NMG is a subgroup of AWMSG which considers the clinical and cost-effectiveness of the medicine, based on written evidence from the applicant company, the AWMSG Secretariat Assessment Report (ASAR), views from clinical experts in the field and relevant patients/carers/patient organisations. NMG makes a preliminary recommendation to AWMSG in relation to each medicine undergoing appraisal. Up to ten NMG meetings are scheduled per year, which are held in private. Is the membership of AWMSG and NMG public? Yes, the membership of AWMSG and NMG is displayed on the AWMSG website. Does AWMSG appraise a medicine if it has been appraised by the Scottish Medicines Consortium (SMC)? Yes, if it meets AWMSG s criteria for appraisal; SMC s advice does not apply to NHS Wales. What is the relationship between AWMSG appraisals and those of the National Institute for Health and Care Excellence (NICE)? AWMSG takes into account the NICE future work programme when considering whether a medicine will be appraised. To avoid duplication of effort, AWMSG would not normally consider undertaking an appraisal if final NICE technology advice (STA or MTA) for the same medicine and indication(s) is expected within 12 months of the date of marketing authorisation. AWMSG advice is interim to that of NICE, should NICE subsequently publish final technology appraisal advice. NICE clinical guidelines are not mandatory within NHS Wales. Page 5 of 21

6 All Wales Medicines Strategy Group Is NICE advice regarding highly specialised technologies (HSTs) mandatory in Wales? No, NICE Highly Specialised Technology (HST) advice is not mandatory within NHS Wales. However, a new process to support the adoption within NHS Wales of relevant commissioning advice issued by the National Institute for Health and Care Excellence (NICE) was introduced in January AWMSG will liaise with the Welsh Health Specialised Services Committee (WHSSC) to consider the applicability of the advice within NHS Wales. AWMSG will subsequently advise Welsh Government on whether the highly specialised technology should be adopted within NHS Wales. What if NICE appraises a medicine but does not recommend its use on the grounds of lack of cost-effectiveness, but the medicine is available to patients living in England via alternative commissioning routes (including the Cancer Drugs Fund)? In January 2014 AWMSG adopted a new approach intended to address some of the issues relating to equity of access in relation to new medicines for patients in Wales. It will apply in circumstances when the National Institute for Health and Care Excellence (NICE) does not recommend a medicine for use within the NHS on the grounds of cost-effectiveness and the medicine is subsequently funded within England via alternative national commissioning routes. An opportunity now exists for the marketing authorisation holder to make an application for the medicine to be appraised by AWMSG. The application will be expected to include a Wales Patient Access Scheme (WPAS), but may also include additional information which may not have been submitted to NICE, or information specific to NHS Wales (perhaps highlighting a specific patient population or other societal benefit/s). It is important that any additional evidence showing added value or benefit to NHS Wales over and above that considered by NICE is clearly identified, highlighted, and reflects the context of an AWMSG appraisal which applies clinical and cost-effectiveness, in addition to a broad strategic, societal and patient perspective to its recommendations. It is also important that confirmation and full details of the alternative funding route within the NHS in England is provided. What communication links exist between the pharmaceutical industry and the All Wales Therapeutics and Toxicology Centre (AWTTC)? Representatives from the pharmaceutical industry regularly meet with representatives from AWTTC to discuss general issues relating to the appraisal process. Individual pharmaceutical companies are encouraged to communicate regularly with AWTTC in relation to future or on-going appraisals. Enquiries should be directed to Mrs Ruth Lang, Head of Liaison & Administration by awttc@wales.nhs.uk or by telephone on How does the AWMSG appraisal process impact on individual prescribers? Individual clinicians should take account of guidance issued by the National Institute for Health and Care Excellence (NICE) or AWMSG when exercising their clinical judgement, unless there is evidence to justify not doing so in the light of particular circumstances of an individual patient. How are potential appraisals identified? The onus for engagement lies with the applicant company to submit Form A. The AWTTC horizon scanning process also informs the AWMSG appraisal process. AWTTC identifies medicines expected to receive marketing authorisation within 18 months and may choose to refer the company to the AWMSG appraisal process. What are the criteria for deciding whether a medicine undergoes an appraisal? AWMSG appraises all new medicines that do not meet AWMSG s exclusion criteria. The decision as to whether a change in indication or formulation is significant and requires appraisal is made by the AWMSG Steering Committee on a case by case basis. November 2015 Page 6 of 21

7 AWMSG Appraisal Process: Frequently Asked Questions What if the criteria for appraisal by AWMSG are not met? Within one month of receipt of Form A, AWTTC will confirm in writing (by or letter) that appraisal by AWMSG is not required. If the application has been declined because it is on the NICE work programme, then the website report of Medicines excluded by AWMSG due to NICE advice will be updated accordingly. The exclusion criteria are designed to provide broad guidance on products which fall outside the role and remit of AWMSG and where progression to formal appraisal is unlikely. In these circumstances Health Boards may consider whether individual products are appropriate for local formulary inclusion. What approach is taken when a medicine has multiple indications? In determining whether a medicine meets the criteria for appraisal, AWTTC will consider the whole licensed indication. In certain circumstances, a pragmatic approach may be adopted and separate appraisals may be undertaken if the licensed indication covers distinctly separate disease areas. Can the applicant company request appraisal of a medicine for part of the licensed indication or in a particular patient population? AWMSG appraise medicines for the full licensed indication(s) as detailed in the Summary of Product Characteristics (SPC). Supporting evidence for the whole of the licensed indication, as agreed in the scope, should be submitted by the applicant company. Where a medicine receives a licence extension, AWMSG will appraise the medicine for the whole of the indication(s) covered by that licence extension. Where the medicine under consideration is newly licensed or has received a licence extension, the applicant company may highlight a specific population within the submission for which the medicine may be particularly advantageous, ensuring that evidence to support the subpopulation is included. In such cases AWMSG may consider a restricted recommendation, whereby the medicine would not be recommended for use outside of this restriction. What if the submission relates to a life-extending, end-of-life medicine? The applicant company should indicate in the submission form whether they consider the AWMSG policy for appraising life-extending, end of life medicines, should be applied and, if so, provide the rationale. Why is the AWMSG Policy on Appraising Life-Extending, End-of-Life Medicines not included in the new process for appraising orphan, ultra-orphan medicines and medicines developed specifically for rare diseases? AWMSG developed a policy for appraising life-extending, end-of-life medicines and this was implemented in It allows for additional criteria to be taken into account by the New Medicines Group (NMG) and the All Wales Medicines Strategy Group (AWMSG) when appraising medicines which are licensed for indications affecting small patient populations with incurable illnesses. In circumstances where NMG does not consider that the additional criteria should be applied and the medicine is not supported for use by NMG, the marketing authorisation holder can request that the appraisal process be suspended and a panel convened to explore the issues in more detail prior to the appraisal by AWMSG. AWMSG s policy for appraising life-extending, end-of-life medicines did not form part of the review of AWMSG s process for appraising orphan, ultra-orphan or medicines developed specifically for rare diseases. At the Stakeholder Meeting when AWTTC first presented its proposals for the new process for appraising orphan, ultra-orphan medicines and medicines developed specifically for rare diseases, it was made clear that inclusion of end of life medicines would cause confusion within the service and, on this basis, end of life medicines were not included. However, it should be noted that the clinician and patient input is a key component of AWMSG s appraisal process and opportunity is extended to patients, patient organisations and carers to highlight advantages and/or disadvantages of all medicines undergoing appraisal. A clinician is routinely invited to attend NMG meetings to set the clinical context and input into the appraisal of all new medicines. Page 7 of 21

8 All Wales Medicines Strategy Group Does AWMSG appraise biosimilar medicines? Where the reference product has been recommended for use by AWMSG or NICE for the same indication(s) and in the same population, or was initially licensed and available prior to 1 st October 2002, and the cost of the new biosimilar medicine is equivalent to or lower than the reference medicine, the application would normally be excluded from appraisal by AWMSG. A full submission will be requested for indication(s)/populations where the reference product had been appraised by AWMSG or NICE and was not recommended for use, or in circumstances where the reference medicine had been licensed post October 2002 and had not been appraised by AWMSG or NICE. Does AWMSG consider equity when appraising a medicine? Yes. AWMSG considers equity of patients within NHS Wales. In addition, when presenting an overview of the submission at the AWMSG public meeting, the AWTTC Appraisal Lead highlights whether the medicine is available in the rest of the UK, either via a commissioning route or via health technology appraisal. This clarification was introduced in In addition, in circumstances where NICE does not recommend a medicine on grounds of lack of cost-effectiveness, but the medicine is available in England via a commissioning route, then the holder of the marketing authorisation may re-engage with AWMSG. The application must include a Wales Patient Access Scheme but may also include additional information not included in the submission to NICE. How does AWMSG prioritise appraisals? Appraisals are scheduled according to the Form B/C submission dates. Prioritising criteria may be applied if the number of appraisal submissions received exceeds the AWMSG meeting capacity. Prioritisation when required will include input from Welsh Clinical Networks, commissioners and others within NHS Wales based on clinical need. When is the appraisal date confirmed? Following submission of Form B/C by the applicant company, AWTTC will confirm by the appraisal scope and schedule. If the AWMSG Steering Committee decides an appraisal is required, what is the timescale? A completed Form B or C can be submitted to the All Wales Therapeutics and Toxicology Centre (AWTTC) before the medicine receives marketing authorisation, and up to three months after. However, it is only on receipt of marketing authorisation that AWTTC will schedule the appraisal and confirm dates of meetings. Potential dates of the New Medicines Group (NMG) and AWMSG meetings will be offered and confirmed with the applicant company. The appraisal process flowchart on the AWMSG website outlines appraisal timelines. The maximum timescale for a limited submission process will be the same as for a full submission, i.e. six months. AWTTC will consult the applicant company should an opportunity arise for a limited submission to be scheduled for appraisal earlier than this; the appraisal may proceed with the earlier timelines following agreement from the applicant company. When is the scope of the appraisal clearly defined? The All Wales Therapeutics and Toxicology Centre (AWTTC) suggests the appraisal scope in writing ( or letter) when they inform the applicant company whether a full submission (Form B) or a limited submission (Form C) is required. The appraisal scope and the dates of the New Medicines Group (NMG) and AWMSG meetings are subsequently confirmed by AWTTC on receipt of Form B/C, following an initial review of the submission for completeness and appropriateness. All attempts to clarify any outstanding issues in relation to the scope should be made by either AWTTC or the applicant company prior to the production of the AWMSG Secretariat Assessment Report (ASAR) and the appraisal by the New Medicines Group (NMG). If NMG considers a redefinition of the scope essential, the appraisal may be adjourned pending clarification. November 2015 Page 8 of 21

9 AWMSG Appraisal Process: Frequently Asked Questions Who do I contact for clarification of the appraisal process or to address any outstanding issues? Clarification of any aspect of the appraisal process may be sought from the All Wales Therapeutics and Toxicology Centre (AWTTC) at: awttc@wales.nhs.uk or on: APPRAISAL SUBMISSION FORMS What is the role of Form A? Form A provides the information required for AWTTC to decide whether a medicine requires appraisal by AWMSG. Form A should be completed for all newly licensed products, each new indication and/or formulation. Form A must be completed regardless of whether the product fits one or more of the exclusion criteria even if a submission has been forwarded to the National Institute for Health and Care Excellence (NICE) or the Scottish Medicines Consortium (SMC). Early submission of Form A is encouraged. It is essential that applicant companies refer to the AWMSG guidance notes for submitting Forms A, B and C available on the AWMSG website at when compiling their submission. Failure to do so may result in an inadequate submission. When should Form A be submitted? Form A should be submitted as early as possible and well before marketing authorisation is received; ideally within one month of receipt of positive opinion from the Committee for Medicinal Products for Human Use (CHMP). Does the Summary of Product Characteristics (SPC) need to be submitted with Form A? Where available, an SPC should be included with the submission (a draft SPC is accepted). However, absence of an SPC does not preclude a company from submitting Form A to the All Wales Therapeutics and Toxicology Centre (AWTTC). What is the timescale for submitting Form B or C? A completed Form B or C can be submitted to the All Wales Therapeutics and Toxicology Centre (AWTTC) before the medicine receives marketing authorisation and up to three months after. An appraisal date will not be scheduled until marketing authorisation is received and the applicant company has provided a complete submission, i.e. Form A and Form B, or Form A and Form C. Does the All Wales Therapeutics and Toxicology Centre (AWTTC) accept unlicensed comparators? The applicant company should provide information on comparator treatment(s) based on current standard care in NHS Wales, i.e. what is considered to be routine practice and may potentially be displaced. Comparators licensed for the indication under consideration should usually be included; however AWMSG will also consider unlicensed comparators where it is deemed appropriate to do so. For some medicines, it may be appropriate to consider more than one comparator (e.g. if practice is varied, or if current therapy is unlicensed). What if the comparator medicine has an associated simple Patient Access Scheme? In order to maintain confidentiality AWMSG will not share the details of a simple patient access scheme for a comparator medicine with the company making an application to AWMSG for appraisal of a new medicine. To enable AWMSG to explore the impact of using the actual cost of the comparator in the analysis, the company applying for appraisal of a new medicine should model the cost-effectiveness of their medicine using a range of potential discounts for the comparator. Page 9 of 21

10 All Wales Medicines Strategy Group Does the All Wales Therapeutics and Toxicology Centre (AWTTC) accept data relating to a licensed comparator outside its licensed dose? AWMSG normally requires comparator data relating to the dose which has been licensed as stated within the Summary of Product Characteristics (SPC). Exceptional circumstances should be discussed in advance of proceeding with the submission. Can the applicant company submit commercial/academic in confidence data? Applicant companies should attempt to minimise the amount of data marked as commercial/academic in confidence provided as part of the Form B or Form C submission, in order to ensure the transparency of the decision making process. If some data are deemed confidential (according to the guidelines agreed by the Association of British Pharmaceutical Industry [ABPI]) it should be clearly marked as such. Information marked Confidential will be made available to members for discussion, but will not be included in the meeting papers uploaded to the AWMSG website. It should be noted that due to the public nature of AWMSG appraisals, commercial/academic in confidence information may be referred to verbally during the formal appraisal. However, where a company is required to respond to extensive questions from AWMSG members about commercial in confidence information during an appraisal held in public, the company may request of the Chair that this will take place within a closed session of the meeting where the public will not be present. Submissions which include a confidential patient access scheme will be appraised by AWMSG in private. What documents will be uploaded to the AWMSG website prior to the AWMSG meeting? The documents placed on the website prior to the AWMSG meeting are the Preliminary Assessment Recommendation (PAR), the company response to the PAR (CR/PAR), a nonconfidential version of the AWMSG Secretariat Assessment Report (ASAR) (sent to the applicant company in advance) and a clinical expert summary (where available). Any commercial/academic in confidence data would be embargoed from the website version until 12 months after completion of the research (patient access schemes will remain confidential). Are the completed submissions (Form A, Form B or Form C) posted on the AWMSG website? No, only basic information from Form A such as generic name, trade name and therapeutic indication is placed on the AWMSG website as part of the Appraisal Work Programme under the Appraisal section, indicating that the medicine has been submitted for consideration. This table also states whether the medicine met the criteria for appraisal by AWMSG. Form B/C is not posted on the AWMSG website. What is the role of Form B/C? Form B/C provides comprehensive information and is used by the All Wales Therapeutics and Toxicology Centre (AWTTC), together with additional relevant information, in the preparation of their assessment report (the AWMSG Secretariat Assessment Report [ASAR]). Form B/C is part of the meeting documentation provided to members of the New Medicines Group (NMG) who make the preliminary appraisal recommendation (PAR) to AWMSG. How does a company know if a medicine requires a full (Form B) or limited (Form C) submission? The nominated contact for the applicant company will be notified by AWTTC in writing whether the submission meets the criteria for AWMSG appraisal and, if so, whether a Form B or Form C is required. AWTTC aim to provide feedback within two weeks and will inform the applicant company if there is a delay. A flow diagram setting out the decision process for a full or limited submission is available on the AWMSG website. The final decision as to whether a full submission (Form B) or limited submission (Form C) is required is that of the AWMSG Steering Committee. A limited submission (Form C) may be November 2015 Page 10 of 21

11 AWMSG Appraisal Process: Frequently Asked Questions deemed appropriate by the AWMSG Steering Committee in any of the following circumstances (where a medicine is not a new chemical entity or for a new licensed therapeutic indication [New Target Disease]): A significant new formulation which has a pro-rata or lower cost per treatment e.g. slow release, new chemical salt of established medicine A licence extension which is deemed minor by the AWMSG Steering Committee e.g. use in paediatrics If the anticipated usage in NHS Wales is considered by the AWMSG Steering Committee to be of minimal budgetary impact If the estimated difference in cost compared with the appropriate comparator(s) is deemed by the AWMSG Steering Committee to be small Follow on biologic medicines, i.e. a biologic product which is identical to an existing product (produced on the same production line in the same factory) but with a different product licence When a limited submission (Form C) is deemed appropriate by the AWMSG Steering Committee, applicant companies may provide less information than routinely required in completion of Form B and aim to prove clinical effectiveness/equivalence. However, evidence of budgetary impact in comparison to the comparator medicine(s) should be demonstrated. Applicant companies should refer to the limited submission process (Form C) and the AWMSG guidance notes on Form C for further information. Applicant companies will be informed in writing ( or letter) whether a full submission (Form B) or a limited submission (Form C) is required, after consideration of Form A. AWMSG reserves the right to request a full submission in relation to any medicine at any time during the process. The decision of the AWMSG Steering Committee in this respect is final and binding. Is guidance available on how to complete Form A, Form B and Form C? Essential information on how to complete all of the submission forms is available under AWMSG guidance notes on the AWMSG website. It is vital that applicant companies refer to this guidance, as failure to do so may result in an inadequate submission. Further advice is available from the All Wales Therapeutics and Toxicology Centre (AWTTC) if required. Where can I find Welsh unit cost data? NHS bodies in Wales produce various annual costing returns which are submitted to the Financial Information Strategy Development Programme (FISDP) for collating on behalf of Welsh Government. The Welsh Costing Return 2 (WCR 2) is one such submission, and provides information on the costs of inpatient and day-case Healthcare Resource Groups (HRGs) at a finished consultant episode (FCE) level and by speciality (e.g. general surgery, cardiology). WCR 2 returns are submitted to FISDP at an elective and emergency level for inpatient activity and consolidated to produce an All Wales average HRG cost per FCE (but not at speciality level). Access to the All Wales average HRG costs per FCE is available to all of the NHS bodies in Wales via the Welsh NHS intranet; or alternatively by contacting the FISDP. The latest information available is the 2007/08 All Wales average HRG costs, which have been produced using version 3.5 HRGs. This means that unlike their English counterparts, they still carry the three-character HRG code (e.g. E28 for cardiac arrest, as opposed to EB05Z, for version 4.0 HRGs). Page 11 of 21

12 All Wales Medicines Strategy Group For information, Wales does not trim its bed days, as in England, and critical care costs are produced as part of the Welsh Costing Return 1 (WCR 1) specialty analysis return. Welsh critical care costs are not included in the HRG costs. Can additional information be provided to the All Wales Therapeutics and Toxicology Centre (AWTTC) after submission of Form B/C? The inclusion of new evidence into the appraisal process after receipt of form B or C is extremely rare and its inclusion is at the discretion of AWTTC, which will be on a case by case basis. AWMSG reserves the right to suspend the appraisal process at any stage in order to seek clarification of an outstanding issue. Form B asks for details of ongoing studies from which additional evidence is likely to be available in the next 6 12 months. If additional information (previously highlighted in that section) becomes available, the applicant company should contact AWTTC who will inform as to whether it can be included in the AWMSG Secretariat Assessment Report (ASAR). This is dependent on timelines. No other information will be accepted. If new evidence is not accepted, a subsequent resubmission will be timetabled pragmatically into the work programme. A resubmission would be timetabled at the earliest convenience; however there is no guarantee of a definite slot and this could take up to 12 months. Would a request for a limited submission (Form C) preclude the need for a full submission (Form B)? AWMSG reserves the right to request a full submission (Form B) in relation to any medicine at any time during the process. The decision of the AWMSG Steering Committee in this respect is final and binding. What if the Form A meets the criteria for a limited submission and the manufacturer has indicated in Form A that they wish to submit a WPAS? This would be assessed on a case by case basis. A limited submission would usually be accepted for a simple WPAS; however a complex scheme would usually require a full submission. Is the process for considering limited submissions (Form Cs) different to that for full submissions (Form Bs)? The New Medicines Group (NMG) considers full and limited submissions and agrees a Preliminary Appraisal Recommendation (PAR). AWMSG subsequently considers full and limited submissions and agrees a Final Appraisal Recommendation (FAR). As the level of detailed information required within a limited submission is less than that of a full submission, the level of discussion will usually be less. Following Ministerial endorsement of the AWMSG recommendation for a limited or full submission, the advice will be posted on the AWMSG website and disseminated electronically to NHS Wales. What are the consequences if a submission (Form A, Form B or Form C) is requested by the All Wales Therapeutics and Toxicology Centre (AWTTC) but not received within the appropriate timelines? Form A should be submitted before marketing authorisation is received, ideally within one month of receipt of positive opinion from the Committee for Medicinal Products for Human Use (CHMP) regardless of whether a submission has been forwarded to the National Institute for Health and Care Excellence (NICE) or the Scottish Medicines Consortium (SMC). The complete submission (i.e. Form A and B or Form A and C) should be submitted to AWTTC as soon as marketing authorisation is granted and, at the very latest, within three months of receipt of marketing authorisation. In the event that a company submission is requested and is not forthcoming, the following two options are available to AWMSG: a) In the absence of a submission from the holder of the marketing authorisation, AWMSG will issue a statement of advice (posted on the AWMSG website) November 2015 Page 12 of 21

13 AWMSG Appraisal Process: Frequently Asked Questions confirming the medicine cannot be endorsed for use within NHS Wales a decision made by the AWMSG Steering Committee. This statement will be ratified by the Minister for Health and Social Services. b) AWMSG will appraise the medicine using publicly available information if directed to do so by officials of the Welsh Government The AWMSG Steering Committee takes into account specialist network opinion, demand from within NHS Wales and policy imperatives when making its decision on how best to proceed with regard to non-submissions. Applicant companies who are planning to submit Form B/C should be aware that appraisal dates cannot be confirmed until the complete submission is received by AWTTC and the appraisal scope has been agreed. A delay in submitting Form B/C will result in a delay in the appraisal process. Funding for use of a medicine that falls within the AWMSG appraisal criteria within NHS Wales is very unlikely prior to an AWMSG appraisal. APPLICANT COMPANY INPUT INTO APPRAISAL PROCESS Does the applicant company have an opportunity to preview the AWMSG Secretariat Assessment Report (ASAR) before it is provided to the New Medicines Group (NMG) members? Yes. The applicant company has a period of ten working days to provide a short summary response to the draft ASAR, i.e. the company response to the ASAR (CR/ASAR). This is the only opportunity for the applicant company to highlight in writing any differences in scientific interpretation and identify factual inaccuracies or typographical errors. No additional clinical or health economic evidence should be submitted (unless previously stated in the Form B/C submission and agreed with the All Wales Therapeutics and Toxicology Centre (AWTTC). The applicant company is also requested to confirm the information which is of a commercial/academic in confidence nature. The CR/ASAR will form part of the NMG appraisal documentation along with the ASAR itself, the Form B/C and written evidence from clinical experts and patient organisation(s) (where available). Failure to provide a response to the draft ASAR by the applicant company will not delay the process. Does the applicant company have an opportunity to preview the Preliminary Appraisal Recommendation (PAR) before it is provided to AWMSG members? Yes. Within five working days of the New Medicines Group (NMG) meeting, the PAR will be forwarded to the applicant company for comment. The company response to the PAR (CR/PAR) will be included with the AWMSG meeting documentation and will be placed on the AWMSG website approximately ten working days before the AWMSG meeting. What is the role of the applicant company in relation to the process for appraising orphan, ultra-orphan medicines and medicines developed specifically for rare diseases? The applicant company will be asked to indicate whether, in their view, the medicine falls within this category (in Form A). If the medicine receives a negative recommendation by NMG, the applicant company can request that a meeting of the Clinician and Patient Involvement Group (CAPIG) be convened. The applicant company will be invited to provide a statement, attend and participate in discussions, and will leave before the finalising of the CAPIG template. Page 13 of 21

14 All Wales Medicines Strategy Group Does the applicant company have an opportunity to preview the final AWMSG Secretariat Assessment Report (ASAR) before it is provided to AWMSG members? Yes. The final ASAR will be forwarded to the applicant company after the New Medicines Group (NMG) meeting for information only. Opportunity to comment on the draft ASAR is afforded to the applicant company before the NMG meeting. In the event that the applicant company provides additional information or comments relating to the final ASAR in their response to the PAR, the All Wales Therapeutics and Toxicology Centre (AWTTC) reserves the right to withhold the response as the additional information/comment(s) would not have been considered by NMG. Failure to provide a response to the PAR by the applicant company will not delay the process. THE PATIENT/CARER VIEW How can patients/carers/patient organisations directly input into the AWMSG appraisal process? The AWMSG appraisal process offers patients/carers/patient organisations an opportunity to ensure their views are heard and provides them with a means to really make a difference. Patients/carers/patient organisations can have a voice in an appraisal process which could ultimately have a significant impact on patients and/or carers living in Wales. An invitation is extended to patients/carers/patient organisations to complete a questionnaire to outline their experience of the disease/condition in question and the associated treatments, and to explain why the needs of the patient/carer are currently met or not met. The All Wales Therapeutics and Toxicology Centre (AWTTC) welcome any information that might help us understand how these health problems affect patients and/or carers. Patients/carers/patient organisations are often able to provide additional insight which is invaluable in considering whether a medicine should be available to patients within NHS Wales. Patients/carers/patient organisations can help inform AWMSG of the real effects on patients and bring a human dimension to the assessment, and this input will have an impact on decisions on which medicines should be funded ahead of a technology appraisal by the National Institute for Health and Care Excellence (NICE). A questionnaire can be downloaded from the AWMSG website and we ask that views be submitted to AWTTC by post or (awttc@wales.nhs.uk) six weeks prior to the New Medicines Group (NMG) meeting in time for all the appraisal information to be collated. The AWMSG meeting is open to the public and patients/carers/patient organisations would be welcome to join the audience. Are all appraisals by AWMSG held in public? There may be occasions where the appraisal of a medicine by AWMSG is held in private. This is usually because the submission made by the holder of the marketing authorisation contains commercially sensitive and confidential information i.e. the submission contains a confidential patient access scheme. Members of the public will not be able to observe that part of the meeting and this will be made clear on the agenda. However, when the meeting recommences in public, the recommendation of AWMSG will be announced. Please contact the All Wales Therapeutics and Toxicology Centre (AWTTC) for further information and/or check the relevant meeting agenda on the AWMSG website for details. Will the completed patient/carer questionnaires be posted on the website? No. The patient/carer questionnaires will not be placed in the public domain. They will, however, be circulated to the New Medicines Group (NMG) and AWMSG members as part of the appraisal meeting documentation. The issues highlighted in the questionnaires may be discussed at the AWMSG meeting in public; however, the patient organisation questionnaires will only be viewed by members. Individual patients/carers submissions will November 2015 Page 14 of 21

15 AWMSG Appraisal Process: Frequently Asked Questions be made anonymous. Patient organisations may also remain anonymous by ticking the relevant box on the questionnaire. How are patient organisations identified and invited to make a submission? The All Wales Therapeutics and Toxicology Centre (AWTTC) use a standard internet search to identify patient organisations. The pharmaceutical company also suggests organisations to contact. AWTTC then invite the relevant patient organisations to fill in a questionnaire. AWTTC also welcomes individual patient views and encourage patients/carers/patient organisations to actively refer to the medicines awaiting your views on the AWMSG website and to complete a questionnaire when appropriate. Why should you, as a patient/carer/patient organisation, provide your views? You can outline your experience of the disease/condition in question and any experience you might have of the associated treatments, explaining why your needs are currently met or not met. We welcome any information that might help us understand how these health problems affect patients and/or carers. Patients/carers/patient organisations are often able to provide additional insight which is invaluable in considering whether a medicine should be available to patients within NHS Wales. You can help inform us of the real effects on patients and bring a human dimension to the appraisal, and this input will have an impact on which medicines should be funded. What should I do if I have any queries or want to learn more about the AWMSG appraisal process? You should telephone or the All Wales Therapeutics and Toxicology Centre (AWTTC) and direct your enquiry to Mrs Ruth Lang, Head of Liaison & Administration. Is there a forum for liaison between AWMSG and patient support groups? The Patient and Public Interest Group (PAPIG) held its first meeting on Wednesday 9 October 2013 in the Academic Centre at University Hospital Llandough. Meetings included discussion about the appraisal processes, medicines development through to clinical trials and patients medicine taking behaviour. Lay representatives from AWMSG and the subgroups have attended and explained their role. PAPIG has considered barriers to engagement with AWMSG and provided feedback on the Patient and Public Engagement (PPE) Strategy. Members have also given feedback on the AWMSG website, which has been redesigned and updated with a section specifically tailored to patients, carers, patient organisations and members of the public. If you are interested in being involved, please contact Ruth Lang on telephone or at awttc@wales.nhs.uk. CLINICAL EXPERTS What is the role of the clinical expert? Clinical experts are contacted by the All Wales Therapeutics and Toxicology Centre (AWTTC) for advice on current practice in NHS Wales and advice on appropriate comparators before inviting a full (Form B) or limited (Form C) submission. On receipt of Form B/C, AWTTC invites clinical experts to submit their views in the form of a questionnaire. Clinical experts set the clinical scene and outline where, in their view, the new medicine sits within current therapy in NHS Wales. How are clinical experts selected? AWMSG seek up to six clinical expert nominations via the appropriate Welsh professional society or clinical network or Medicines and Therapeutics Committees (MTCs). In the absence of appropriate expertise in NHS Wales, AWMSG will seek clinical input from outside Wales. Page 15 of 21